Philippe JEAN-PIERRE

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• Type de publi. : Article dans une revue
• Date de publi. : 01/12/2020
• Auteurs : Adil SoualyDavid DeutschMourad BenallaouaAmal Ait-OmarFlorence MarySabine HelfenMarouane BoubayaVincent LevyRobert BenamouzigRobert BenamouzigFlorence MaryAmal Aït OmarMourad BenallaouaSabine HelfenSemaher Al-KhafajiNoémie DemareGéraldine PerkinsPierre Laurent-PuigJean-Christophe SaurinNaouele RabyLaurence Venat-BouvetCorinne PenaudDelphine BonnetVirginie SicartChloé PomesThierry LecomteClaire JollivetMorgane CauletStanislas ChaussadeMarion DhoogeFanny MaksimovicPhilippe GrandvalSylvie OlschwangMaud SaussereauJérôme BellangerAnne Netter-CotiHélène DelhomelleBruno BuecherLydia MehdiSophie LejeuneAfane BrahimiStéphane CattanLaurence BellengierDavid TougeronSandrine RafertEmmanuelle Barouk SimonetFrançois CornelisAnna Serova-ErardDavid MalkaPaul GestaJeanne OddozVéronique MariSamuel LesourdGaëlle KergoatLouise CrivelliIradj SobhaniAurélien AmiotCôme LepageLaurence Faivre-OlivierJean-Louis JouveAntoine DrouillardNora PerotMarc BardouSophie NambotNadia MekahliAlain LortholaryCarole LenneJean-Paul LagasseBrahim OuahraniThierry FrébourgNathalie ParodiMaud BranchaudFrançoise DesseigneElodie GrinandOlivier IngsterBenoit SemelinFrancine FeinNelson LourencoThomas AparicioMathilde BrasseurAnthony Lopez
• Organismes : Signalisation, Microenvironnement et Hémopathies Lymphoïdes B
• Publié dans Trials le 31/10/2020

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Résumé : Abstract Lynch syndrome (LS) is the most common cause of inherited colorectal cancer (CRC) and confers a high lifetime risk of CRC estimated to be up to 60%. Colonoscopy is recommended every 2 years in LS patients above the 20–25-year-old age bracket, and every year when colonic neoplasia has been detected. Efficient chemoprevention has the potential to represent a cost-effective intervention in these high-risk patients and could allow a delay in colonoscopy surveillance. Several epidemiological studies have shown that regular use of low dose aspirin is associated with a 20 to 30% reduction in the risk of sporadic colonic adenomas and colorectal cancer regardless of family risk. However, in recent large randomized trials in specific populations, aspirin use showed no protection for colorectal cancer. A prospective randomized CAPP-2 trial evaluated the effect of aspirin use in LS patients. The primary analysis of this trial showed no significant decrease in CRC in LS patients under daily aspirin. However, a preplanned secondary analysis after an extended follow-up showed a significant reduced risk of CRC in the aspirin group in the per-protocol analysis. The real effect and clinical benefit of aspirin are still to be consolidated in this population. The AAS-Lynch trial—a prospective, multicentric, double-blind, placebo-controlled, randomized clinical trial—was designed to investigate if daily aspirin therapy, at a dose of 100 or 300 mg, would decrease the occurrence or recurrence of colorectal adenomas in patients under 75 years of age, compared with placebo. Trial registration ClinicalTrials.gov NCT02813824 . Registered on 27 June 2016. The trial was prospectively registered.

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Fichiers liés : main.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/12/2020
• Auteurs : Benjamin TerrierRaphaël DarbonCécile-Audrey DurelÉric HachullaAlexandre KarrasHélène MaillardThomas PapoXavier PuéchalGrégory PugnetThomas QuéméneurMaxime SamsonCamille TailleLoïc GuillevinVincent AudardOlivier AumaîtreKarine BriotPatrice CacoubPascal CathébrasDominique ChauveauOlivier ChosidowLaurent ChouchanaVincent CottinDivi Yk CornecEric DaugasElisabeth DiotNicolas DupinKhalil El KarouiOlivier FainPierre GobertPhilippe GuilpainMohamed HamidouAurelie HummelMarie JachietStephane JouneauNoémie Jourde-ChicheCédric LandronClaire Le JeunneJean‐christophe LegaXavier MarietteNathalie MorelChristian PagnouxPhilippe RemyFrederic Vandergheynst
• Organismes : Service de médecine interne et centre de référence des maladies rares [CHU Cochin] Association France Vascularites [Paris] Hospices Civils de Lyon Centre Hospitalier Régional Universitaire [CHU Lille] Institute for Translational Research in Inflammation - U 1286 Service de Néphrologie et Hémodialyse [CHU HEGP] Centre Hospitalier Régional Universitaire [CHU Lille] AP-HP - Hôpital Bichat - Claude Bernard [Paris] Service de médecine interne et centre de référence des maladies rares [CHU Cochin] Centre Hospitalier Universitaire de Toulouse Centre hospitalier [Valenciennes, Nord] Service de Médecine Interne (SOC 1 et SOC 2) [CHU de Dijon] AP-HP - Hôpital Bichat - Claude Bernard [Paris] Service de médecine interne et centre de référence des maladies rares [CHU Cochin] Hôpital Henri Mondor, Assistance Publique - Hôpitaux de Paris IMRB - PGD/"Pathophysiology of Glomerular Diseases" [Créteil] CHU Gabriel Montpied [Clermont-Ferrand] Nutritional Epidemiology Research Team | Equipe de Recherche en Epidémiologie Nutritionnelle Hôpital Cochin [AP-HP] Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] Institut des Maladies Métaboliques et Cardiovasculaires Département de Néphrologie et Transplantation d'organes [CHU Toulouse] Hôpital Henri Mondor Hôpital Cochin [AP-HP] Hospices Civils de Lyon Université Claude Bernard Lyon 1 Lymphocytes B, Autoimmunité et Immunothérapies CHRU Brest - Service de Rhumatologie AP-HP - Hôpital Bichat - Claude Bernard [Paris] Centre Hospitalier Régional Universitaire de Tours Hôpital Cochin [AP-HP] Université Paris Descartes - Paris 5 IMRB - PGD/"Pathophysiology of Glomerular Diseases" [Créteil] CHU Saint-Antoine [AP-HP] Hôpital Privé de Provence [Aix-en-Provence] Centre Hospitalier Régional Universitaire [Montpellier] Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB) Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Hopital Saint-Louis [AP-HP] Hopital Saint-Louis [AP-HP] Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Université de Rennes
• Publié dans Orphanet Journal of Rare Diseases le 27/10/2020

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Résumé : Systemic necrotizing vasculitis comprises a group of diseases resembling polyarteritis nodosa and anti-neutrophil cytoplasmic antibody-associated vasculitis (ANCA): granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, and microscopic polyangiitis. The definitive diagnosis is made in cooperation with a reference center for autoimmune diseases and rare systemic diseases or a competency center. The management goals are: to obtain remission and, in the long term, healing; to reduce the risk of relapses; to limit and reduce the sequelae linked to the disease; to limit the side effects and the sequelae linked to the treatments; to improve or at least maintain the best possible quality of life; and to maintain socio-professional integration and/or allow a rapid return to school and/or professional activity. Information and therapeutic education of the patients and those around them are an integral part of the care. All health professionals and patients should be informed of the existence of patient associations. The treatment of vasculitis is based on variable combinations of glucocorticoids and immunosuppressants, chosen and adapted according to the disease concerned, the severity and/or extent of the disease, and the underlying factors (age, kidney function, etc.). Follow-up clinical and paraclinical examinations must be carried out regularly to clarify the progression of the disease, detect and manage treatment failures and possible relapses early on, and limit sequelae and complications (early then late) related to the disease or treatment. A distinction is made between the induction therapy, lasting approximately 3-6 months and aimed at putting the disease into remission, and the maintenance treatment, lasting 12-48 months, or even longer. The role of the increase or testing positive again for ANCA as a predictor of a relapse, which has long been controversial, now seems to have greater consensus: Anti-myeloperoxidase ANCAs are less often associated with a relapse of vasculitis than anti-PR3 ANCA.

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Fichiers liés : s13023-020-01621-3.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/12/2020
• Auteurs : Matthieu TalagasN. LebonvalletRaphael LeschieraGerard SinquinPhilippe EliesMarek HaftekJean‐pierre PennecDenis RessnikoffVeronica La PadulaRaphaele Le GarrecKillian L'HerondelleOlivier MignenLaëtitia Le PottierNathalie KerfantAlexia ReuxPascale MarcorellesLaurent Misery
• Organismes : Laboratoire sur les interactions Epithéliums Neurones Laboratoire sur les interactions Epithéliums Neurones Laboratoire sur les interactions Epithéliums Neurones Laboratoire Mouvement Sport Santé Laboratoire sur les interactions Epithéliums Neurones Laboratoire sur les interactions Epithéliums Neurones Lymphocytes B, Autoimmunité et Immunothérapies Lymphocytes B, Autoimmunité et Immunothérapies Centre Hospitalier Régional Universitaire de Brest Laboratoire sur les interactions Epithéliums Neurones Laboratoire sur les interactions Epithéliums Neurones Laboratoire sur les interactions Epithéliums Neurones Centre Hospitalier Régional Universitaire de Brest
• Publié dans Annals of Neurology le 26/10/2020

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Résumé : Objective: Pain, temperature, and itch are conventionally thought to be exclusively transduced by the intraepidermal nerve endings. Although recent studies have shown that epidermal keratinocytes also participate in sensory transduction, the mechanism underlying keratinocyte communication with intraepidermal nerve endings remains poorly understood. We sought to demonstrate the synaptic character of the contacts between keratinocytes and sensory neurons and their involvement in sensory communication between keratinocytes and sensory neurons. Methods: Contacts were explored by morphological, molecular, and functional approaches in cocultures of epidermal keratinocytes and sensory neurons. To interrogate whether structures observed in vitro were also present in the human epidermis, in situ correlative light electron microscopy was performed on human skin biopsies. Results: Epidermal keratinocytes dialogue with sensory neurons through en passant synaptic-like contacts. These contacts have the ultrastructural features and molecular hallmarks of chemical synaptic-like contacts: narrow intercellular cleft, keratinocyte synaptic vesicles expressing synaptophysin and synaptotagmin 1, and sensory information transmitted from keratinocytes to sensory neurons through SNARE-mediated (syntaxin1) vesicle release. Interpretation: By providing selective communication between keratinocytes and sensory neurons, synaptic-like contacts are the hubs of a 2-site receptor. The permanent epidermal turnover, implying a specific en passant structure and high plasticity, may have delayed their identification, thereby contributing to the long-held concept of nerve endings passing freely between keratinocytes. The discovery of keratinocyte-sensory neuron synaptic-like contacts may call for a reassessment of basic assumptions in cutaneous sensory perception and sheds new light on the pathophysiology of pain and itch as well as the physiology of touch.

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• Type de publi. : Article dans une revue
• Date de publi. : 01/12/2020
• Auteurs : Sandrine VinaultAnne-Sophie MarietMaëlle Le BrasEric MiralliéCatherine Cardot-BautersFrançois PattouPhilippe RuszniewskiAlain SauvanetPhilippe ChansonEric BaudinDominique EliasFabrice MenegauxSebastien GaujouxFrançois Borson-ChazotJean-Christophe LifantePhilippe CaronNicolas CarrereAntoine TabarinChristophe LaurentMarc KleinLaurent BrunaudPatricia NiccoliFrédéric SebagGuillaume CadiotReza KianmaneshMaxime LuuC BinquetPierre Goudet
• Organismes : Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques Lipides - Nutrition - Cancer [Dijon - U1231] Université Bourgogne Franche-Comté [COMUE] Service Biostatistiques et Informatique Médicale (CHU de Dijon) Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques Service d'Endocrinologie [Nantes] Service de Chirurgie Digestive et Endocrinienne [Nantes] Service Endocrinologie, diabétologie, maladies métaboliques et nutrition Recherche translationnelle sur le diabète - U 1190 Département de chirurgie endocrinienne [Lille] Service de Gastroentérologie [Hôpital Beaujon] Centre de recherche sur l'Inflammation Service de chirurgie hepato-pancreato-biliaire Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique Service d'Endocrinologie et des Maladies de la Reproduction [AP-HP Hôpital de Bicêtre] Médecine nucléaire [Gustave Roussy] Institut Gustave Roussy CHU Pitié-Salpêtrière [AP-HP] CHU Pitié-Salpêtrière [AP-HP] Chirurgie digestive, hépato-biliaire et endocrinienne [CHU Cochin] Health Service and Performance Research Département Endocrinologie-Diabétologie-Maladies Nutritionnelles [Lyon-Sud] Health Service and Performance Research Service de chirurgie digestive et endocrinienne (centre hospitalier Lyon Sud) Service Endocrinologie, maladies métaboliques et nutrition [CHU Toulouse] Pôle Maladies de l'appareil digestif [CHU Toulouse] Centre Hospitalier Universitaire de Bordeaux Centre Hospitalier Universitaire de Bordeaux Service d'Endocrinologie [CHRU Nancy] Service de Chirurgie Digestive Hépatobiliaire et Endocrine [CHRU Nancy] Institut Paoli-Calmettes Service de chirurgie générale et endocrinienne Hôpital universitaire Robert Debré [Reims] Hôpital universitaire Robert Debré [Reims] Plateforme d’Investigation Technologique [Centre d’Investigation Clinique 1432 module Plurithématique - Dijon] Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques Lipides - Nutrition - Cancer [Dijon - U1231] Université Bourgogne Franche-Comté [COMUE] Service de Chirurgie Digestive, Cancérologique, Générale, Endocrinienne et Urgences (CHU de Dijon) Lipides - Nutrition - Cancer [Dijon - U1231] Université Bourgogne Franche-Comté [COMUE]
• Publié dans Annals of Surgery le 26/10/2020

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Résumé : Objective: To assess the distant metastatic potential of duodeno-pancreatic neuroendocrine tumors (DP-NETs) in patients with MEN1, according to functional status and size. Summary Background Data: DP-NETs, with their numerous lesions and endocrine secretion-related symptoms, continue to be a medical challenge; unfortunately they can become aggressive tumors associated with distant metastasis, shortening survival. The survival of patients with large nonfunctional DP-NETs is known to be poor, but the overall contribution of DP-NETs to metastatic spread is poorly known. Methods: The study population included patients with DP-NETs diagnosed after 1990 and followed in the MEN1 cohort of the Groupe d’étude des Tumeurs Endocrines (GTE). A multistate Markov piecewise constant intensities model was applied to separate the effects of prognostic factors on 1) metastasis, and 2) metastasis-free death or 3) death after appearance of metastases. Results: Among the 603 patients included, 39 had metastasis at diagnosis of DP-NET, 50 developed metastases during follow-up, and 69 died. The Markov model showed that Zollinger-Ellison-related tumors (regardless of tumor size and thymic tumor pejorative impact), large tumors over 2 cm, and age over 40 years were independently associated with an increased risk of metastases. Men, patients over 40 years old and patients with tumors larger than 2 cm, also had an increased risk of death once metastasis appeared. Conclusions: DP-NETs of 2 cm in size or more, regardless of the associated secretion, should be removed to prevent metastasis and increase survival. Surgery for gastrinoma remains debatable.

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• Type de publi. : Article dans une revue
• Date de publi. : 01/12/2020
• Auteurs : Guillaume HerpeMathieu NaudinMathieu LederlinFarida EnikeevaOlivier BoumendilLucie CassagnesMadeleine CavetKathia ChaumoitrePhilippe FeuersteinIsabelle FittonViolaine FloryCornelia Anna FreitagJean-Yves GaubertJules GregoryHubert NivetMickaël OhanaIsabelle PetitNicolas SansMathilde WagnerRémy GuillevinPierre-Jean SaulnierJean-Michel BartoliJean-Pierre TasuJean-Paul Beregi
• Organismes : Service de radiologie [CHU de Poitiers] Data Analysis and Computations Through Imaging Modeling-Mathématiques, Imagerie, Santé Data Analysis and Computations Through Imaging Modeling-Mathématiques, Imagerie, Santé Service de radiologie et imagerie médicale [Rennes] = Radiology [Rennes] Data Analysis and Computations Through Imaging Modeling-Mathématiques, Imagerie, Santé TELEDIAG Service Imagerie Médicale et Radiologie Interventionnelle - site Gabriel-Montpied [CHU Clermont-Ferrand] Auteur indépendant Département de Radiologie [Hôpital de la Timone - APHM] Groupe hospitalier de la région de Mulhouse et Sud-Alsace Hôpital Européen Georges Pompidou [APHP] Hôpital Pasteur [Nice] Centre Hospitalier Universitaire de Nîmes Département de Radiologie [Hôpital de la Timone - APHM] Hôpital Beaujon [AP-HP] IMADIS Nouvel Hôpital Civil de Strasbourg Département de Radiologie adultes [CHRU Nancy] Pôle imagerie médicale [CHU Toulouse] Sorbonne Université Service de radiologie [CHU de Poitiers] CIC de Poitiers – Centre d'investigation clinique de Poitiers (CIC 1402) Département de Radiologie [Hôpital de la Timone - APHM] Service de radiologie [CHU de Poitiers] Centre Hospitalier Universitaire de Nîmes
• Publié dans European Radiology le 23/10/2020

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Résumé : Purpose To determine the impact of the COVID-19 on the CT activities in French radiological centers during the epidemic peak. Materials and methods A cross-sectional prospective CT scan survey was conducted between March 16 and April 12, 2020, in accordance with the local IRB. Seven hundred nine radiology centers were invited to participate in a weekly online survey. Numbers of CT examinations related to COVID-19 including at least chest (CTcovid) and whole chest CT scan activities (CTchest) were recorded each week. A sub-analysis on French departments was performed during the 4 weeks of the study. The impact of the number of RT-PCRs (reverse transcriptase polymerase chain reactions) on the CT workflow was tested using two-sample t test and Pearson’s test. Results Five hundred seventy-seven structures finally registered (78%) with mean response numbers of 336 ± 18.9 (323; 351). Mean CTchest activity per radiologic structure ranged from 75.8 ± 133 (0–1444) on week 12 to 99.3 ± 138.6 (0–1147) on week 13. Mean ratio of CTcovid on CTchest varied from 0.36 to 0.59 on week 12 and week 14 respectively. There was a significant relationship between the number of RT-PCR performed and the number of CTcovid (r = 0.73, p = 3.10−16) but no link with the number of positive RT-PCR results. Conclusion In case of local high density COVID-19, CT workflow is strongly modified and redirected to the management of these specific patients.

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Fichiers liés : s00330-020-07035-w.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/12/2020
• Auteurs : Margot SmirdecMercé JourdainVirginie GuastellaCéline LambertJean-Christophe RichardLaurent ArgaudSamir JaberKada KloucheAnne MedardJean ReignierJean-Philippe RigaudJean-Marc DoiseRussell ChabanneBertrand SouweineJeremy BourenneJulie DelmasPierre-Marie BertrandPhilippe VerdierJean-Pierre QuenotCécile AubronNathanael EisenmannPierre AsfarAlexandre FrataniJean DellamonicaNicolas TerziJean-Michel ConstantinAxelle ManevalRenaud GuerinBruno PereiraAlexandre Lautrette
• Organismes : CHU Clermont-Ferrand Recherche translationnelle sur le diabète - U 1190 CHU Clermont-Ferrand Service Biostatistiques, Télématiques, Traitement de l’image [CHU Clermont-Ferrand] Service d'Anesthésie et de Soins Intensifs [Hôpital de la Croix-Rousse - HCL] Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé Modeling & analysis for medical imaging and Diagnosis Hôpital Edouard Herriot [CHU - HCL] Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] Centre Hospitalier Régional Universitaire [Montpellier] Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] Centre Hospitalier Régional Universitaire [Montpellier] CHU Clermont-Ferrand Hôtel-Dieu de Nantes Centre hospitalier de Dieppe Centre Hospitalier Chalon-sur-Saône William Morey CHU Clermont-Ferrand CHU Clermont-Ferrand Hôpital de la Timone [CHU - APHM] Centre Hospitalier Rodez Centre Hospitalier de Cannes Hôpital de Montluçon Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand Centre Hospitalier Régional Universitaire de Brest Centre Jean Perrin [Clermont-Ferrand] Centre Hospitalier Universitaire d'Angers Hopital Saint-Louis [AP-HP] Centre Hospitalier Universitaire de Nice Centre Hospitalier Universitaire [CHU Grenoble] CHU Pitié-Salpêtrière [AP-HP] AutomédiCation aCcompagnement Pluriprofessionnel PatienT Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) CHU Clermont-Ferrand Service Biostatistiques, Télématiques, Traitement de l’image [CHU Clermont-Ferrand] CHU Clermont-Ferrand Centre Jean Perrin [Clermont-Ferrand] Laboratoire Microorganismes : Génome et Environnement
• Publié dans Critical Care le 31/10/2020

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Résumé : Background: There is wide variability between intensivists in the decisions to forgo life-sustaining treatment (DFLST). Advance directives (ADs) allow patients to communicate their end-of-life wishes to physicians. We assessed whether ADs reduced variability in DFLSTs between intensivists.Methods: We conducted a multicenter, prospective, simulation study. Eight patients expressed their wishes in ADs after being informed about DFLSTs by an intensivist-investigator. The participating intensivists answered ten questions about the DFLSTs of each patient in two scenarios, referring to patients' characteristics without ADs (round 1) and then with (round 2). DFLST score ranged from 0 (no-DFLST) to 10 (DFLST for all questions). The main outcome was variability in DFLSTs between intensivists, expressed as relative standard deviation (RSD).Results: A total of 19,680 decisions made by 123 intensivists from 27 ICUs were analyzed. The DFLST score was higher with ADs than without (6.02 95% CI [5.85; 6.19] vs 4.92 95% CI [4.75; 5.10], p < 0.001). High inter-intensivist variability did not change with ADs (RSD: 0.56 (round 1) vs 0.46 (round 2), p = 0.84). Inter-intensivist agreement on DFLSTs was weak with ADs (intra-class correlation coefficient: 0.28). No factor associated with DFLSTs was identified. A qualitative analysis of ADs showed focus on end-of-life wills, unwanted things and fear of pain.Conclusions: ADs increased the DFLST rate but did not reduce variability between the intensivists. In the decision-making process using ADs, the intensivist's decision took priority. Further research is needed to improve the matching of the physicians' decision with the patient's wishes.

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Fichiers liés : s13054-020-03402-7.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/12/2020
• Auteurs : Mariano A. OstuniPatricia HermandEmeline SaindoyNoëlline GuillouJulie GuellecAudrey CoensClaude HattabElodie Desuzinges-MandonAnass JawhariSoria Iatmanen-HarbiOlivier LequinPatrick FuchsJean-Jacques LacapèreC. CombadiereFrederic PincetPhilippe Deterre
• Organismes : Centre d'Immunologie et de Maladies Infectieuses Centre d'Immunologie et de Maladies Infectieuses Immunologie et Embryologie Moléculaires Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) Institut de Biologie Intégrative de la Cellule Centre d'Immunologie et des Maladies Infectieuses Dynamique des Structures et Interactions des Macromolécules Biologiques Centre National de la Recherche Scientifique CALIXAR Centre de recherche sur l'Inflammation Université Pierre et Marie Curie - Paris 6 Laboratoire de Spectroscopies et Structures Biomoléculaires (LSSBM) Centre de recherche biomédicale Bichat-Beaujon Centre d'Immunologie et de Maladies Infectieuses Yale School of Medicine [New Haven, Connecticut] Mécanismes Moléculaires Membranaires Centre d'Immunologie et de Maladies Infectieuses
• Publié dans Scientific Reports le 26/10/2020

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Résumé : During inflammatory response, blood leukocytes adhere to the endothelium. This process involves numerous adhesion molecules, including a transmembrane chemokine, CX3CL1, which behaves as a molecular cluster. How this cluster assembles and whether this association has a functional role remain unknown. The analysis of CX3CL1 clusters using native electrophoresis and single molecule fluorescence kinetics shows that CX3CL1 is a homo-oligomer of 3 to 7 monomers. Fluorescence recovery after photobleaching assays reveal that the CX3CL1-transmembrane domain peptide self-associates in both cellular and acellular lipid environments, while its random counterpart (i.e. peptide with the same residues in a different order) does not. This strongly indicates that CX3CL1 oligomerization is driven by its intrinsic properties. According to the molecular modeling, CX3CL1 does not associate in compact bundles but rather with monomers linearly assembled side by side. Finally, the CX3CL1 transmembrane peptide inhibits both the CX3CL1 oligomerization and the adhesive function, while its random counterpart does not. This demonstrates that CX3CL1 oligomerization is mandatory for its adhesive potency. Our results provide a new direction to control CX3CL1-dependent cellular adherence in key immune processes. The migration of blood leukocytes to damaged tissues is the first step of the inflammation process and involves a sequence of coordinated interactions between leukocytes and endothelial cells 1-3. The chemotactic cytokines called chemokines that primarily attract leukocytes, are central to the physiological and pathological inflamma-tory processes 4-6. Chemokines trigger leukocyte activation and their firm adhesion to the inflamed endothelium, mainly through integrins 7-9. Two members of the chemokine family are exceptions: CXCL16 and CX3CL1. In addition to their chemokine domain (CD), these two chemokines possess three domains: a mucin-like stalk, a transmembrane (TM) domain, and a cytosolic tail 10,11. When interacting with their cognate receptors (CXCR6 and CX3CR1, respectively), these chemokines induce cell-cell adhesion 12. CXCL16 and CX3CL1 can also be cleaved by metalloproteinases, such as ADAM10 and ADAM17 13-15 , to produce a soluble form with chemotactic functions. The CX3CL1 chemokine, with its unique CX3CR1 receptor 16 , is involved in adherence to the endothelium of the inflammatory monocyte population (CD14 hi CD16-CX3CR1 + CCR2 + in humans, Ly6C hi CX3CR1 + CCR2 + in mice) 12,17-20 likely through interaction with platelets 21,22. This chemokine is also involved in the recruitment of NK lymphocytes 23,24 and in lymphocyte survival as in allergic diseases 25 , as well as in monocytic 26,27 and neuronal survival 28-31. An additional function of the CX3CR1-CX3CL1 pair is the regulation of the patrolling behavior and the margination of monocytes in blood vessels 32,33 or their adherence to the bone marrow 34. The CX3CL1 chemokine is also involved in cytoadhesion of red blood cells infected with the malaria parasite Plasmodium

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Fichiers liés : Ostuni-ScRep_2020_Complet.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/12/2020
• Auteurs : Lidia DelrieuEmmanuelle JacquetCéline Segura-FerlayEllen BlancOlivia Febvey-CombesChristine FriedenreichGilles RomieuWilliam JacotMaria RiosPierre-Etienne HeudelCélia Roemer-BecuweChristelle JouannaudOlivier TredanLoïc ChaigneauMonica ArnedosHubert OrfeuvreNathalie Quenel-TueuxJean-Philippe JacquinJean-Marc FerreroIsabelle MoulletSophie Abadie-LacourtoisieFrédérique Penault-LlorcaDavid CoxThomas Bachelot
• Organismes : Centre Hospitalier Universitaire [CHU Grenoble] Centre de Recherche en Cancérologie de Lyon Centre Léon Bérard [Lyon] Imagerie Moléculaire et Stratégies Théranostiques Centre Jean Perrin [Clermont-Ferrand]
• Publié dans Scientific Reports le 26/10/2020

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Résumé : Benefits of physical activity are widely demonstrated for early stage cancers but few studies have focused on metastatic disease. The purpose of this study was to determine the impact of physical activity on survival in patients with metastatic breast cancer. We conducted a secondary analysis of the national, multicentric, non-randomized, prospective cohort SNPs to Risk of Metastasis (StoRM) study. The level of physical activity was self-reported at inclusion and divided into three categories of physical activity: light level, moderate level, and vigorous level. Overall, 833 patients (56.2%) completed the physical activity questionnaire at baseline on average physical activity during the previous year: 11.6% had a light level of physical activity, 69.0% achieved moderate levels of physical activity and 19.3% reported vigorous levels of physical activity. After adjustment for confounding, physical activity was not statistically significantly associated with overall survival in the whole population. Subgroup analysis identified that both vigorous and moderate physical activity were associated with statistically significantly improved overall survival compared to light physical activity level only in the HER2 positive subgroup (HR 0.23; 95% CI 0.07-0.70, p = 0.01 and HR 0.38; 95% CI 0.15-0.96, p = 0.04). Physical activity done during the previous year was associated with survival in HER2 positive metastatic breast cancer patients. These results suggest that overall survival in metastatic breast cancer patients could be improved through physical activity which should be considered as a complementary intervention for these individuals. The study showed that moderate/vigorous levels of physical activity were associated with better overall survival, and that these associations remained statistically significant in multivariate analysis in the HER2 positive subgroup. These results have clinical relevance and justify the recommendations for physical activity interventions in metastatic breast cancer.

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• Type de publi. : Article dans une revue
• Date de publi. : 01/12/2020
• Auteurs : Pierre Le Balc'HKieran PinceauxCharlotte PronierPhilippe SeguinJean-Marc TadiéFlorian Reizine
• Organismes : Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Biosit : biologie, santé, innovation technologique Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Biosit : biologie, santé, innovation technologique Université de Rennes - Faculté de Médecine Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Université de Rennes - Faculté de Médecine Biosit : biologie, santé, innovation technologique Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Université de Rennes - Faculté de Médecine Biosit : biologie, santé, innovation technologique
• Publié dans Critical Care le 31/10/2020

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Fichiers liés : s13054-020-03252-3

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• Type de publi. : Article dans une revue
• Date de publi. : 01/12/2020
• Auteurs : Pierre Francois LesaultGrégoire RangeRadwan HakimFarzin BeyguiDenis AngoulvantPierre MarcolletMatthieu GodinRonan DeballonPhilippe BonnetOlivier FichauxChristophe BarbeyLouis ViallardPierre Francois LesaultEric DurandEmmanuel BoiffardGerard DutheilJean‐philippe ColletHakim BenamerPhilippe CommeauGilles MontalescotRene KoningPascal Motreff
• Organismes : Hôpital privé de l'Estuaire [Le Havre] Hôpitaux de Chartres [Chartres] Hôpitaux de Chartres [Chartres] Service de cardiologie et de pathologie vasculaire [CHU Caen] CHU Trousseau [Tours] Centre Hospitalier Jacques Coeur [Bourges] Clinique Saint-Hilaire [Rouen] Pôle santé Oréliance UFR Institut de psychologie [Sociétés et Humanités] - Université Paris Cité Centre Hospitalier Regional d'Orléans Nouvelle Clinique Tourengelle Centre Hospitalier Henri Mondor d'Aurillac Hôpital privé de l'Estuaire [Le Havre] Hôpital Charles Nicolle [Rouen] Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon Clinique Bergougnian CHU Pitié-Salpêtrière [AP-HP] Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases Clinique de la Roseraie Polyclinique des fleurs CHU Pitié-Salpêtrière [AP-HP] Clinique Saint-Hilaire [Rouen] CHU Clermont-Ferrand
• Publié dans Journal of the American College of Emergency Physicians Open le 07/01/2021

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Résumé : Objectives The aim of this study was to assess the impact of the coronavirus disease 2019 (COVID‐19) outbreak on incidence, delays, and outcomes of ST‐elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI) in France. Methods We analyzed all patients undergoing PPCI <24 hours STEMI included in the prospective France PCI registry. The 2 groups were compared on mean monthly number of patients, delays in the pathway care, and in‐hospital major adverse cardiac events (MACE: death, stent thrombosis, myocardial infarction, unplanned coronary revascularization, stroke, and major bleeding). Results From January 15, 2019 to April 14, 2020, 2064 STEMI patients undergoing PPCI were included: 1942 in the prelockdown group and 122 in the lockdown group. Only 2 cases in the lockdown group were positive for COVID‐19. A significant drop (12%) in mean number of STEMI/month was observed in the lockdown group compared with prelockdown (139 vs 122, P < 0.04). A significant increase in “symptom onset to first medical contact” delay was found for patients who presented directly to the emergency department (ED) (238 minutes vs 450 minutes; P = 0.04). There were higher rates of in‐hospital MACE (7.7% vs 12.3%; P = 0.06) and mortality (4.9% vs 8.2%; P = 0.11) in the lockdown group but the differences were not significant. Conclusion According to the multicenter France PCI registry, the COVID‐19 outbreak in France was associated with a significant decline in STEMI undergoing PPCI and longer transfer time for patients who presented directly to the ED. Mortality rates doubled, but the difference was not statistically significant.

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Fichiers liés : emp2.12325.pdf

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